1. Field of the Invention
The present invention relates to use of substituted guanidines and other compounds for use in treatment of eye disease, particularly retinal ischemia and trauma, optic nerve disorders and trauma, and related eye disorders and trauma.
2. Background
Retinal ischemia or degeneration may be produced by injury, tumors or the like, or be associated with various disorders such as where occlusion of a blood vessel or elevated intraocular pressure reduces availability of blood, oxygen or other nutrients to the retina or optic nerve which can result in neuronal cell death (degeneration) and loss of vision. Such disorders include e.g. diabetes, atherosclerosis, venous capillary insufficiency, obstructive arterial and venous retinopathies, glaucoma, diabetic retinopathy and senile macular degeneration. Optic nerve injury and damage also can result in vision loss and can arise from a variety of conditions or incidents.
Certain therapies have been reported to alleviate such disorders. For example, certain calcium blockers have been reported for use in treating disorders arising from poor blood flow in the eye. See U.S. Pat. No. 5,431,907. Other therapies have included use of fibrinolytic agents and anticoagulants. See U.S. Pat. No. 4,795,423. However, such treatments have had limited effectiveness.
It thus would be desirable to have new agents for treatment of retinal ischemia and trauma, optic nerve injury and associated disorders.
The present invention includes methods for treatment of eye disorders and injury, including methods for treatment of reduced flow of blood or other nutrients to retinal tissue or optic nerve, methods for treatment of retinal ischemia and trauma and associated disorders, and methods for treatment for optic nerve injury/damage. Disorders associated with retinal or optic nerve injury or ischemia that may be treated in accordance with the invention include e.g. diabetes, atherosclerosis, venous capillary insufficiency, obstructive arterial or venous retinopathies, senile macular degeneration, cystoid macular edema and glaucoma.
The present methods in general comprise administering a therapeutically effective amount of one or more substituted guanidines or other compounds as described below to a patient in need of treatment, such as a mammal suffering from or susceptible to retinal ischemia or injury or trauma, or optic nerve injury or trauma, or associated disorder.
Compounds useful in the methods of the invention have been disclosed in U.S. Pat. No. 4,906,779 (Weber et al.; issued Mar. 6, 1990); U.S. Pat. No. 5,011,834 (Weber et al.; issued Apr. 30, 1991); U.S. Pat. No. 5,093,525 (Weber et al.; issued Mar. 3, 1992); U.S. Pat. No. 5,190,976 (Weber et al.; issued Mar. 2, 1990); U.S. Pat. No. 5,262,568 (Weber et al.; issued Nov. 16, 1993); U.S. Pat. No. 5,403,861 (Goldin et al.; issued Apr. 4, 1995); and International Applications PCT/US91/03594 (Keana et al.; International Publication No. WO 91/18868); PCT/US92/0105 (Goldin et al.; International Publication No. WO 92/14697); PCT/US92/03554 (Weber et al.; International Publication No. WO 92/19621); PCT/US94/06008 (Durant et al.; International Publication No. WO 94/27591); PCT/US94/13245 (Durant et al.; International Publication No. WO 95/14461); PCT/US94/13541 (Magar et al.; International Publication No. WO 95/14467); and PCT/US95/01536 (Goldin et al.; International Publication No. 95/20950). Each of those documents and the substituted guanidines and other therapeutic compounds disclosed therein are fully herein by reference. Thus, for example, preferred compounds for use in present methods include substituted guanidines include N,Nxe2x80x2-disubstituted guanidines, N,N,Nxe2x80x2-trisubstituted guanidines and N,N,Nxe2x80x2,Nxe2x80x2-tetrasubstituted guanidines.